Synthesis, characterisation and in vitro investigation of photodynamic activity of 5-(4-octadecanamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride on HeLa cells using low light fluence rate

Malatesti, Nela; Harej, Anja; Pavelić, Sandra Kraljević; Lončarić, Martin; Zorc, Hrvoje; Wittine, Karlo; Andjelković, Uroš; Josić, Djuro

doi:10.1016/j.pdpdt.2016.07.003

Cited by 18 publications

(43 citation statements)

References 44 publications

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“…The amphiphilic and completely water-soluble porphyrin with tricationic pyridinium-3-yl groups and a very lipophilic 4-octadecanamidophenyl group at the fourth meso-position was used in PDT on HeLa cell line, and it exhibited significantly higher phototoxicity than the hydrophilic counterpart bearing a 4-acetamidophenyl group instead of the one with a long alkyl chain. These two cationic porphyrins had almost identical, photophysical properties, but different logP and hydrophilic-lipophilic balance (HLB), and subsequently very different PDT activity, thus confirming the importance of the lipophilicity on the cellular uptake and overall PDT efficiency (Malatesti et al 2016). Four cationic Zn(II) phthalocyanines with different lengths of the alkyl side-chain ranging from (methyl)-pyridyloxy to (dodecyl)-pyridyloxy were used for the photoinactivation of Aeromonas hydrophila, and the study showed that both the accumulation and the PDT efficacy increases with the length of the alkyl chain (Kussovski et al 2009).…”

Section: Lipophilicity and Cellular Uptakementioning

confidence: 90%

“…The length of the alkyl chain has a strong impact on aggregation, and pyridinium porphyrins with longer alkyl chains (C8, C12 and C18) have been shown to form micelles (Dancil et al 1997). Nevertheless, aggregation is generally not so problematic for cationic amphiphilic porphyrins because they usually start to aggregate in concentrations higher than 10 −5 M, while a good PS is expected to be PDTefficient in concentrations < 10 −6 M (Malatesti et al 2016;Simões et al 2016). …”

Section: Ps Distributionmentioning

confidence: 99%

“…However, several reports have shown their beneficial features in vitro: low dark toxicity, better selectivity for malignant cells, and higher efficiency compared to their hydrophilic PS analogues (Tovmasyan et al 2014;Malatesti et al 2016). They are known to have favourable pharmacokinetic properties (Henderson et al 1997), and were found to be promising in in vitro and in vivo cancer models (Faudale et al 2012;Rapozzi et al 2014).…”

Section: Pdt and The Immune System Pdt-mediated Immune Responses In Cmentioning

confidence: 99%

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Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

2017

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Photodynamic therapy (PDT) combines a photosensitiser, light and molecular oxygen to induce oxidative stress that can be used to kill pathogens, cancer cells and other highly proliferative cells. There is a growing number of clinically approved photosensitisers and applications of PDT, whose main advantages include the possibility of selective targeting, localised action and stimulation of the immune responses. Further improvements and broader use of PDT could be accomplished by designing new photosensitisers with increased selectivity and bioavailability. Porphyrin-based photosensitisers with amphiphilic properties, bearing one or more positive charges, are an effective tool in PDT against cancers, microbial infections and, most recently, autoimmune skin disorders. The aim of the review is to present some of the recent examples of the applications and research that employ this specific group of photosensitisers. Furthermore, we will highlight the link between their structural characteristics and PDT efficiency, which will be helpful as guidelines for rational design and evaluation of new PSs.

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Section: Lipophilicity and Cellular Uptakementioning

confidence: 90%

Section: Ps Distributionmentioning

confidence: 99%

Section: Pdt and The Immune System Pdt-mediated Immune Responses In Cmentioning

confidence: 99%

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Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

2017

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“…In our previous study, we prepared 5‐(4‐octadecanamidophenyl)‐10,15,20‐tris( N ‐methylpyridinium‐3‐yl)porphyrin trichloride ( TMPyP3‐C 17 H 35 ) and a comparison of this amphiphilic PS with the hydrophilic analogue 5‐(4‐acetamidophenyl)‐10,15,20‐tris( N ‐methylpyridinium‐3‐yl)porphyrin trichloride ( TMPyP3‐CH 3 ) revealed that the lipophilic moiety significantly improved PDT efficiency . We decided to continue our focus on similar tripyridyl porphyrins, especially to investigate further the effect of the long alkyl chain.…”

Section: Resultsmentioning

confidence: 99%

“…The longer alkyl chains were shown to facilitate cellular uptake, thus difference in saturation could have a different impact on the interactions of PSs with the cell membrane based on its fluidity. Therefore, we prepared TMPyP3‐C 17 H 33 as an analogue of TMPyP3‐C 17 H 35 that contains an unsaturated alkyl chain derived from oleoyl chloride instead of a stearoyl chain in the latter, using the same synthetic procedures as previously described . The only variation was applied in the methylation step in which CH 2 Cl 2 /MeOH was used as a solvent instead of DMF.…”

Section: Resultsmentioning

confidence: 99%

In Vitro Photodynamic Activity of N‐Methylated and N‐Oxidised Tripyridyl Porphyrins with Long Alkyl Chains and Their Inhibitory Activity in Sphingolipid Metabolism

et al. 2018

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A series of N-methylated and N-oxidised tripyridyl porphyrins were synthesised, characterised, and their PDT activity was studied with six cell lines. All the tested porphyrins with a long alkyl chain, except one, were more efficient for PDT than an N-methylated hydrophilic porphyrin and N-oxidised porphyrin without the long alkyl chain. Generally, N-methylated tripyridyl porphyrins were more active than those N-oxidised, but IC values for phototoxicity of two N-oxides, named TOPyP3-C H O and TOPyP3-C H , were still in the nanomolar concentration range for most of the tested cell lines. However, TOPyP3-C H did not show phototoxicity on human foreskin fibroblast cells. Two methylated amphiphilic porphyrins, named TMPyP3-C H and TMPyP4-C H showed significant dark toxicity, whereas none of the oxidopyridyl porphyrins were toxic without light activation. The selected photosensitisers were shown to be apoptosis inducers, and had inhibitory effects on the clonogenic growth of HCT116 and HeLa cells. All three N-methylated amphiphilic porphyrins significantly reduced the migratory potential of HCT116 cells. Porphyrins TMPyP3-C H and TOPyP3-C H reduced the activity of acid ceramidase, whereas TOPyP3-C H O had a significant inhibitory effect on sphingosine kinase 1 activity in HeLa cells. Compounds with this dual activity were shown to be the most promising photosensitisers, with potential to treat invasive cancers.

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Water‐Soluble Zinc Porphyrin Capable of Light‐Induced Photocleavage of DNA: Cell Localization Studies in Drosophila Melanogaster and Light Activated Treatment of Lung Cancer Cells

et al. 2016

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A new water‐soluble zinc(II) porphyrin has been synthesized and characterized by high resolution mass spectroscopy, elemental analysis, and electronic absorption spectroscopy. The zinc(II) porphyrin (ZnPor) is designed with three N‐methylated pyridyl groups at the meso‐positions to make the compound water soluble. In addition, a meso‐pentafluorophenyl substituent has been incorporated to enhance the excited state lifetime of the porphyrin. The addition of zinc(II) into the porphyrin core lends itself to longer excited lifetimes as well as the ability to coordinate to DNA bases exposed in the major groove. The ZnPor and its free‐base analog (FBPor) demonstrate high binding affinity to calf thymus DNA (ctDNA) with binding constants greater than 100000 m–1. Both porphyrins show the ability to photonick DNA when irradiated within the photodynamic therapy window (600–850 nm); however, ZnPor shows enhanced photoreactions and the ability to cause double strand breaks. Under hypoxic conditions only ZnPor is capable of causing single strand breaks when irradiated with visible light. Both ZnPor and FBPor are nontoxic to the lung cancer cell line A549 in the dark at concentrations as high as 100 µm but show cytotoxicity to A549 cells at concentrations as low as 75 nm when irradiated with visible light. Studies of the ZnPor in Drosophila melanogaster indicate statistically insignificant toxicity when compared to control at concentrations well above the light‐induced toxicity levels. Evidence for localization of ZnPor in the nuclei of the Drosophila salivary gland cells suggests a mechanism for cellular transport, which may prove beneficial in PDT treatment.

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Synthesis, characterisation and in vitro investigation of photodynamic activity of 5-(4-octadecanamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride on HeLa cells using low light fluence rate

Cited by 18 publications

References 44 publications

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

In Vitro Photodynamic Activity of N‐Methylated and N‐Oxidised Tripyridyl Porphyrins with Long Alkyl Chains and Their Inhibitory Activity in Sphingolipid Metabolism

Water‐Soluble Zinc Porphyrin Capable of Light‐Induced Photocleavage of DNA: Cell Localization Studies in Drosophila Melanogaster and Light Activated Treatment of Lung Cancer Cells

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